Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased levels of an endogenous inhibitor of tissue-plasminogen activator (t-PA) have been thought to relate to the genesis of acute myocardial ischemia. To examine the role of the rapid inhibitor of t-PA, plasma samples were analyzed from 75 patients with chest pain syndrome undergoing coronary angiography (mean age 57 years), 24 patients with clinically documented coronary artery disease (unstable angina, positive exercise stress test or previous history of myocardial infarction; mean age 58 years) and 15 young normal subjects (mean age 26 years). Plasma t-PA inhibitor levels were similar in age-matched patients regardless of the absence or presence (and degree) of coronary artery disease. Plasma t-PA inhibitor levels correlated significantly with age (r - 0.46, p less than 0.005), suggesting an age-dependent decrease in fibrinolytic activity. Plasma t-PA inhibitor levels also correlated significantly with serum triglyceride levels (r - 0.60, p less than 0.001), but not with coronary risk factors such as serum cholesterol, diabetes, hypertension, serum uric acid levels or body weight. Association of high levels of inhibitor of t-PA with hypertriglyceridemia may be of importance in the development of coronary thrombosis, especially in elderly patients. Nonetheless, this study does not suggest a pathogenic role of t-PA inhibitor in coronary atherosclerosis.
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PMID:Plasma tissue plasminogen activator inhibitor levels in coronary artery disease: correlation with age and serum triglyceride concentrations. 310 May 98

The direct and indirect actions of two active components of slow-reacting substance of anaphylaxis, leukotrienes C4 (LTC4) and D4 (LTD4), were studied in chronically instrumented unanesthetized sheep. Intravenous injection of 3 micrograms of LTD4 caused immediate marked pulmonary arterial hypertension which returned to baseline in 6.5 +/- 1.0 min. Dynamic compliance of the lungs (Cdyn) and left atrial (PLA) and aortic (Paorta) blood pressure fell concomitantly with the increases in pulmonary artery pressure (PPA). PLA and Paorta then increased above baseline and heart rate deceased significantly. LTD4 caused only small increases in lung lymph flow but did increase lung lymph concentrations of thromboxane B2. Lung lymph concentrations of 6-keto-prostaglandin F1 alpha did not increase following LTD4 infusion. The increase in PPA after 3-micrograms injections of LTD4 was greater than that caused by 10-micrograms injections of prostaglandin H2-analog. Injections of 10-30 micrograms of LTC4 caused only minor increases in PPA but did cause bradycardia and delayed increases in PLA and Paorta. The cyclooxygenase inhibitors meclofenamate and ibuprofen inhibited the increases in PPA caused by LTD4 but not the later bradycardia or increases in PLA and Paorta. The thromboxane synthetase inhibitor UK-38485 attenuated the early increase in PPA and moderated the later increases in PLA and Paorta and bradycardia caused by LTD4 injection. The response of unanesthetized sheep to LTD4 is mediated, at least in part, indirectly by stimulation of the cyclooxygenase pathway of arachidonate metabolism.
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PMID:Direct and indirect effects of leukotriene D4 on the lungs of unanesthetized sheep. 311 26

Twenty-two patients were selected from a group of 33 patients who underwent recombinant human tissue-type plasminogen activator (rt-PA) thrombolysis for thrombosed infrainguinal bypass grafts of the lower extremity and were compared with 38 matched patients who had undergone surgical thrombectomy during the same period. The proportion of persons with diabetes mellitus, smokers, and types of bypass grafts was similar in both groups. More patients in the rt-PA-treated group had hypertension (p = 0.01). To evaluate the different lengths of follow-up, Kaplan-Meier survival analysis was used with a log-rank test to compare the proportion of persons with patent grafts in the two treatment groups. At 30 days, 86% of the rt-PA-treated grafts were still patent compared with 42% of the surgically treated grafts (p = 0.001). When risk factors on the Kaplan-Meier curves were compared, there was no statistical difference with regard to graft patency among the groups. According to simultaneous Cox regression analysis, no risk factor was significantly associated with graft patency. When amputation was evaluated between treatment groups simultaneously with other risk factors in a logistic regression analysis, smoking and age of the graft were marginally significant (p = 0.07), whereas all other factors were clearly not significant. In 91% of the rt-PA-treated patients, a secondary surgical procedure was required to maintain patency of the graft segment. Eighty-nine percent of the surgically treated patients required similar graft revisions. Two patients in the surgical group and one patient in the rt-PA-treated group had major complications.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thrombolysis of peripheral arterial bypass grafts: surgical thrombectomy compared with thrombolysis. A preliminary report. 312 19

In eight male patients with normal liver and kidney function fibrinolytic components were measured in arterial blood and in renal and hepatic vein blood, obtained during catheterization for analysis of hypertension. Blood samples were collected simultaneously from veins und corresponding arteries before and 5 minutes after the completion of intravenous injection of desmopressin (DDAVP), 0.4 micrograms/kg body weight over a 10 minute period. DDAVP induced a rise in t-PA antigen and activity, and in von Willebrand factor, accompanied by a decrease in free PA-inhibitor level. We failed to detect a significant rise in plasma urokinase activity. The concentrations of fibrinogen, plasminogen, alpha 2-antiplasmin, antithrombin III and coeruloplasmin did not change either. Renal production of t-PA under basal conditions was inferred from a negative arterio-venous (A-V) difference in t-PA-activity and in t-PA-antigen levels but this could not be confirmed by orthogonal regression analysis of the same data. A-V differences of other fibrinolytic factors were negligible. In the hepatic vessels a significant positive A-V difference of t-PA-activity and of t-PA-antigen levels was a uniform finding. After DDAVP, when plasma levels were elevated, the mean A-V difference was proportionally higher, consistent with a constant fractional elimination rate. Free PA-inhibitor was virtually absent from arterial blood after DDAVP, but appeared in hepatic vein blood, indicating either production of the inhibitor by the liver or dissociation of a circulating complex of t-PA and its inhibitor in the liver. The blood levels of the other investigated components did not show any change upon passage through the liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal and hepatic handling of endogenous tissue-type plasminogen activator (t-PA) and its inhibitor in man. 314 78

In diseases associated with thrombotic or thromboembolic complications, a reduction in the fibrinolytic potential may contribute to the risk to develop thrombosis. To investigate whether juvenile cerebral infarction is associated with a permanent defect of the fibrinolytic system we measured the main components of the fibrinolytic system, tissue plasminogen activator (t-PA) and its fast acting inhibitor (PAI) in plasma samples of 21 patients (aged 21-44 years) 3-24 months after the acute event. The data obtained were compared to those from thirteen healthy young volunteers (22-46 years). A direct effect of known risk factors on the fibrinolytic system could be excluded because patients avoided their risk factors immediately after the ischemic cerebral attack. Hypertension and the combination of oral contraceptives and smoking had been the most striking original risk factors. Levels of t-PA antigen and t-PA activity before and after venous occlusion, or PAI activity were not different between patients and controls suggesting that at least a permanent decrease in the activity of the fibrinolytic system does not exist in these patients. However, our findings do not exclude that a temporary defect in fibrinolysis might have contributed to the acute onset of the thrombotic cerebral event possibly induced by the risk factors originally present.
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PMID:[Persistent changes in tissue-type plasminogen activator and plasminogen activator inhibitor fibrinolytic parameters in patients following juvenile ischemic cerebral infarct]. 314 88

The pyrrolizidine alkaloid monocrotaline produces pulmonary inflammation, hemorrhage, fibrosis, and hypertension. In rats, monocrotaline pneumotoxicity can be ameliorated by cotreatment with inhibitors of angiotensin converting enzyme (ACE), such as CL242817. In the present study, serum and urine copper (Cu) concentrations were evaluated as indices of cardiopulmonary injury in rats sacrificed after six weeks of continuous administration of monocrotaline (0 to 3.6 mg per kg per day, in the drinking water) or CL242817 (60 mg per kg per day, in the feed), or both. Monocrotaline-treated rats exhibited dose-dependent increases in (1) pulmonary histopathology, (2) pulmonary endothelial dysfunction (decreased lung plasminogen activator activity, and increased prostacyclin and thromboxane production), (3) pulmonary hydroxyproline (collagen) content, and (4) cardiac right ventricular hypertrophy (an anatomic correlate of pulmonary hypertension). The severity of cardiopulmonary damage was accompanied by a dose-dependent elevation in serum Cu concentration. Serum iron concentration, in contrast, did not change. Urinary Cu concentration correlated roughly with that of serum, but the variability within groups was high. Cotreatment with the ACE inhibitor CL242817 not only ameliorated monocrotaline-induced right heart enlargement and lung hydroxyproline accumulation but also reduced the hypercupremia in monocrotaline-treated rats. Thus, serum copper concentration appears to be an accurate and minimally invasive index of monocrotaline pneumotoxicity in this model of pulmonary hypertension.
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PMID:Serum copper concentration as an index of cardiopulmonary injury in monocrotaline-treated rats. 314 70

Clinical and pathological findings in 15 autopsy cases, 13 males and 2 females, confirming cardiac free wall rupture after AMI were reported. The incidence is 30.6% of all autopsy cases of AMI in Chinese PLA General Hospital from 1958 to 1979. The ages ranged from 46 to 79 years, 10 being above 60 years. For 73.3% it was the first AMI and 66.7% of the patients had a history of hypertension. Thirteen of the 15 patients died within 5 days after the onset of AMI and another 2 within 7 days. When the cardiac rupture occurred, the ECG generally showed bradycardia, AV-junctional rhythm, III degrees AV block or isorhythmic ventricular rhythm and cardiac arrest. Both the gross and microscopic AMI were examined in 13 cases. All of them had a septal infarct, but only 2 had an ECG diagnosis. Of the 6 patients with inferior MI on ECG, 5 had right and left coronary lesions worse than grade III. The effective prevention of cardiac rupture consists of early diagnosis, control of chest pain and vomiting, prevention or treatment of hypertension or hypotension and 1 to 2 weeks of bed rest after the onset of AMI.
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PMID:Cardiac free wall rupture after acute myocardial infarction. Clinical and pathological analysis. 383 11

A highly active angiotensin-producing enzyme (enzyme II) was obtained from dog serum by acid treatment and fractionation to remove angiotensinase and converting enzyme, separate an inhibitor, and convert an inactive precursor (proenzyme II) to enzyme II. Proenzyme II was found to be converted to enzyme II by an endogenous activating enzyme identified as plasmin. Conversion was also caused by the interaction of bacterial streptokinase with human proactivator, by trypsin, and by an activator formed from liver tissue extract and dog serum. Neither plasma kallikrein nor the labile, human extrinsic tissue-type plasminogen activator induced activation. The inhibitor, which normally blocks the activation of proenzyme II, was unusually stable against high temperatures and extremes of pH, and it was not identical to any of the six known protease inhibitors of serum. Enzyme II was not identical to other angiotensin-producing enzymes such as enzyme I, renin, cathepsin D, pepsin, plasmin, tonin, or cathepsin G. Enzyme II reacted maximally at pH 4.7 and produced up to 2250 ng of angiotensin I/ml serum/hr from the substrate of dog serum (i.e., amounts 3200-fold higher than that produced by endogenous renin of normal dog serum). Since at pH 7.2, angiotensin I formation is still about 30 times higher than that of renin, enzyme II may be physiologically active under some conditions.
Hypertension
PMID:Angiotensin-producing serum enzyme II. Formation by inhibitor removal and proenzyme activation. 390 15

Fibrinogen, fibrinogen-related antigen (FR-antigen), and components of the fibrinolytic enzyme system were measured in patients with essential hypertension, renal disease with and without hypertension, and normal subjects. Essential hypertension was associated with a decrease in plasminogen activator and an increase in FR-antigen. In renal disease these changes were accompanied by increases in plasminogen activation inhibitor, alpha(2)-macroglobulin, alpha(1)-antitrypsin, and fibrinogen.
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PMID:The fibrinolytic enzyme system in hypertension. 471 59

A patient with systemic lupus erythematosus had severe hypertension, rapidly worsening renal failure, and multiple successive thrombotic cerebrovascular and retinal lesions develop. In a kidney biopsy specimen luminal thrombi were demonstrated in arteries and arterioles, without vasculitic or inflammatory changes. The patient's plasma was markedly deficient in both prostacyclin stimulating factor (PSF) and vascular plasminogen activator (VPA), and also contained a potent inhibitor of in vitro urokinase-induced fibrinolysis. Treatment with ancrod resulted in striking reversal of the progressive renal damage and clinical recovery from the thrombotic cerebrovascular and retinal lesions. This clinical improvement was associated with improved renal histologic appearance, correction of the PSF and VPA deficiencies, and disappearance of the urokinase inhibitor. Possible mechanisms of action of ancrod are discussed.
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PMID:Ancrod in systemic lupus erythematosus with thrombosis. Clinical and fibrinolysis effects. 622 28


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